Figure 2.

Mechanisms of rhythm generation in cardiomyocytes based on a model by Maltsev et al. (85). Two loops, an external membrane loop and an internal calcium loop independently ensure the generation of impulses. Therefore, they provide some redundancy, but they are also intertwined at the stage of slow L-type Ca²⁺ current (I_CaL) activation. Thyroid hormone signaling is able to modulate both loops simultaneously via interfaces at several sites (75, 81, 86–91), and direct myocardial effects of TSH are largely opposing (92). g_K, ionic conductance for K⁺; INCX, Na⁺/Ca²⁺ exchange current; I_CaT, T-type Ca2+ current; I_f, hyperpolarisation-activated “funny” current; I_K, voltage-gated K⁺ current; I_st, sustained non-selective current; I_to, transient outward potassium current; LCR, local Ca²⁺ release; SERCA, sarcoendoplasmic reticulum Ca²⁺-ATPase; SR, sarcoplasmic reticulum.